J Formos Med Assoc. 2026 Sep 17:S0929-6646(26)00906-X. doi: 10.1016/j.jfma.2026.09.021. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiac involvement is a common presentation of late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This study explored phenotypes of cardiac amyloidosis and their clinical and neurological correlates in the premanifest stage.
METHODS: Premanifest carriers with the transthyretin p.A117S variant were enrolled. Healthy controls and ATTRv-PN patients with stage 1 polyneuropathy disability (PND) were enrolled for comparison. The risk of cardiomyopathy was estimated by the Mayo ATTR-CM score, and cardiomyopathy was evaluated by echocardiography, 99mTc-pyrophosphate (PYP) single-photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum natriuretic peptide (NT-proBNP). Neuropathy was assessed using clinical questionnaires, skin biopsy, neurophysiology, and quantitative sensory testing.
RESULTS: Thirty-two premanifest carriers with transthyretin variants (31 p.A117s) were enrolled, along with 63 controls and 11 ATTRv-PN patients (9 p.A117S). None of the carriers had polyneuropathy or showed high-risk Mayo ATTR-CM score, while 38% had carpal tunnel syndrome and 16% had increased radiotracer uptake on 99mTc-PYP SPECT imaging. Compared with controls, carriers demonstrated a greater extracellular volume (ECV), longer myocardial native T1, and greater left ventricular mass index on CMR, indicating subclinical cardiac amyloidosis. ATTRv-PN patients had markedly greater amyloid burden across these cardiac imaging. Among carriers, CMR parameters and 99mTc-PYP SPECT uptake were significantly correlated with nerve degeneration. Higher 99mTc-PYP SPECT uptake was associated with increased NT-proBNP, native T1, ECV, autonomic and sensory dysfunction, and presence of CTS.
CONCLUSIONS: Subclinical cardiomyopathy, as shown by nuclear medicine imaging and CMR, is common and linked to neuropathic changes among ATTRv-PN premanifest carriers carrying predominant p.A117S variant, and may facilitate early and accurate diagnosis and intervention for ATTRv-PN.
PMID:42754478 | DOI:10.1016/j.jfma.2026.09.021